The present invention relates to measuring backscatter waveforms behavior in time due to ultrasound excitement of tissue to determine tissue type or substance composition, and more particularly, to a method, and corresponding device and system thereof, using ultrasound waves for tissue substance differential excitation, that creates different scattering behavior changes when exciting different tissues or substances; and measuring the backscatter waveform behavior before, while, and/or after excitation periods, at one or more locations in the tissue, and measuring gradients of this behavior, to image the examined area and/or determine tissue types or substance composition irregularities.
There are many situations where it is necessary or desirable to identify tissue nature and substance in an organ. One example of such a situation is the identification of malignant areas within the body of a patient, where it is required to first find the exact location of suspected cancerous region for sampling, and then indicate whether the suspected location is in fact cancerous, and if so of what malignant nature. Other such situations include the ability to visualize a map of tissue types or substance composition for medical imaging purposes. Yet another example is the need for reading different substance levels within a body, such as glucose levels in the blood.
In these and other cases it is desirable to determine tissue irregularities for localizing suspected material, image tissues, or analyze the tissue substance. It is also desirable to identify, or find the probability of identification of, tissue as of known characteristics.
Present techniques known from the prior art for determining tissue type or substance include medical imaging, and tissue sampling such as a blood sample or to biopsy techniques. Imaging of tissue type or substance and irregularities include technologies such as X-Ray, MRI, PET, Ultrasound, and IR imaging. X-Ray based tomography uses high energy electromagnetic radiation that is harmful to both patient and physician. This harmful effect substantially reduces the capacity of this technology to enable continues imagery. As X-Ray technology mainly measures acid levels in the examined area, it is limited to identifying desirable tissue differences where acid levels substantially differ. MRI uses high intensity magnetic fields. As such it yields very high cost of ownership. The need for very accurate magnetic field in MRI equipment substantially limits the geometry of the equipment, not enabling desirable physician interaction with the body of the patient at affordable costs. PET technology is limited in its capacity to identify desirable substance composition differences, and hence is used mainly in conjunction with other imaging techniques.
Ultrasound-diagnostics equipment mostly analyzes ultrasound waves' specular reflection; as such it is limited in its capacity to identify desirable tissue substance as sonic echo does not differentiate well enough between tissue materials. Table 1, a table of ultrasound speed and acoustic impedence for different soft tissues, taken from G. E. P. M. Van Venrooij, “Measurement of ultrasound velocity in human tissue,” Ultrasonics, October 1971, p. 240-242, shows that specular reflection coefficients, due to differences in acoustic impedance between soft tissues, are typically only a few times 10−4, or less, which is typically below the noise level.
TABLE 1Ultrasound velocity, density, characteristic impedance and reflectioncoefficient of normal brain tissue of some body fluids and brain tumorsNumber ofTmeasuringcerrorθZRSubstance[° C.]points N[ms−1][%][kgm−3][106 Nsm−3][×105]Sourcewater (not23.5201493.50.1997.411.4896—θ fromdegassed)handbook ofChemistry andPhysics 1968/69blood23.2101549.60.710361.6053Heparinisedblood24.2111556.40.310411.6219samples fromblood {close oversize brace} 22.61015701.510531.65343four differentblood22.4121565810361.6211patientsCSF24.491515310061.52447Fresh samplesCSF {close oversize brace} 25111509.50.510061.51954from threeCSF21.8111499210051.50662different patientsmeningioma19201524.20.4———After three hoursimmersion informalinemeningioma19.8201524.50.510311.5720.3After forty-eighthours immersionin formalineependymoma20181501310241.53717Formalisedastrocytoma24.9271517810791.6418samplesglioma22.3171500310261.53922glioma22.2201529.10.610211.5616Fresh samplesastrocytoma27.5411545.40.4———meningioma19.72015572———Five differentmeningioma19.72015461———slides of onemeningioma {close oversize brace} 19.72115692———tumourmeningioma19.71415482———meningioma19.71415692.5———
Advanced ultrasound techniques use other characteristics of the echo reflectance in the body, such as ultrasonic backscatter of power waves for elasticity measurement, however those too are not sufficient for clear differentiation between different tissue types or substances in the examined organs.
Arthur et al, in a talk “Change in Ultrasonic Backscattered Energy for Temperature Imaging: Factors Affecting Temperature Accuracy and Spatial Resolution in 3-D,” presented at the 32nd UITC, Alexandria, Va., May 16, 2007, describe tests they did to develop a technique for using changes in backscattered energy of ultrasound to produce 3-D temperature maps in soft tissue, in order to monitor hyperthermia cancer treatment. The authors calculate theoretically that the standard deviation in backscattering energy, from place to place in a liver tissue sample with many small inclusions of aqueous or lipid material, increases monotonically with temperature, and they present in vitro test results with samples of bovine liver, turkey breast, and pork muscle, that confirm their calculations. They predict that it should be possible to use this technique to measure temperature to within 0.5 degrees Celsius, with a spatial resolution of 1 cm, for some kinds of tissue, if the tissue is calibrated.
Seip and Ebbini, “Noninvasive Estimation of Tissue Temperature Response to Heating Fields Using Diagnostic Ultrasound,” IEEE Transactions on Biomedical Engineering, vol 42, pp. 828-839 (1995), describe another technique for using backscattering of diagnostic ultrasound to monitor temperature changes in tissue. The technique is based on the observation that most biological tissues are semi-regular scattering lattices. Muscle tissue, for example, may have a semi-regular lattice structure due to individual muscle fibers, with spacing on the order of 1 mm. These lattice structures produce harmonics in the backscattered ultrasound, with the frequency shift of the harmonics depending on temperature, through the temperature dependence of the sound speed, and the thermal expansion of the lattice structure. If the temperature dependence of the sound speed, and the thermal expansion coefficient, are known for the type of tissue being tested, then changes in the frequency shift can be used to measure changes in temperature. Autoregressive model-based methods are used to estimate the frequency shift. The authors state that temperature can be measured, using this technique, to within 0.4 degrees Celsius, with a spatial resolution of 1 mm. To achieve this precision, the lattice spacing, the temperature dependence of sound speed, and the thermal expansion coefficient of the tissue must all be known a priori. However, the technique could still be used to measure a relative temperature response, even if the temperature dependence of sound speed and the thermal expansion coefficient of the tissue are not known very accurately.
IR imagery is used to map the tissue's natural heat superficially, however due to the mammal natural heat control mechanisms, temperature is equalized by in-vivo tissues as heat conduction and convection occur within the organ, hence this technology is very limited in its capacity to identify desirable tissue substance.
Other means of identifying tissue substance composition include sampling tissue out of the organ for analysis. These include blood samples, biopsy, and others. The limitation of such technologies is in the need to sample out tissue from the organs, sometimes without knowing whether the sample is taken from the correct position inside the organ. Other limitations are the required handling, and the fact it is analyzed out of the living organ after loosing some of its characteristics. These currently available techniques from the prior art hence enable less than desirable functionality of real time imaging/identification or differentiation of in-vivo tissue. In particular, X-Ray harmful effects could be substantially reduced if there was to exist a harmless method for imaging in-vivo tissue at high resolution, with flexible equipment geometry, at affordable costs. Additionally, it would be preferable if there was to exist a method and system for imaging of tissue that could substantially differentiate between different tissues in an organ, and enable the identification of malignant tumors, or other irregularities in live tissue.
Blood sampling techniques known form the prior art are based on drawing of blood from the body and lack the ability of identifying the point in time where glucose levels non-linearly change from acceptable levels. In particular, the identification of time of change, could be significantly enhanced if there was to exist a capacity to conduct on going monitoring of the glucose level with non-intrusive means.
US 2004/0030227 to Littrup et al describes a method for treating a medical pathology including receiving a first set of acoustic radiation scattered by a volume of tissue containing at least a portion of the medical pathology, and thereafter, changing a temperature of the volume of tissue. The method also includes thereafter, receiving a second set of acoustic radiation scattered by the volume of tissue and localizing the portion of the medical pathology from the first and second sets of received acoustic radiation. Localizing the portion of the medical pathology comprises identifying the medical pathology from differences in the first and second sets of received acoustic radiation resulting from the change in temperature. In some embodiments, the change in temperature is produced by ultrasound heating. The method also includes insonifying the portion of the medical pathology with sufficient energy to damage the portion of the medical pathology. Littrup et al also describe heating breast tissue with RF power, and using thermoacoustic computed tomography to detect tumors, relying on the greater heating response of tumors over benign tissue.
U.S. Pat. No. 6,728,567 to Rather et al, which was a priority document for Littrup et al, describes using an array of ultrasound transducers, transmitting ultrasound through body tissue from different directions, to find the ultrasound absorption rate, the sound speed, and other parameters, as a function of three-dimensional position in the body tissue, using tomographic methods. The results are used to distinguish cancerous tissue from healthy tissue.
US 2009/0105588 to Emelianov et al, describes heating tissue with lasers, though ultrasound heating is mentioned as well, and using ultrasound to measure the temperature change and determine whether it is fat or muscle, from the fact that fat and muscle have different thermal expansion coefficients, and different rates of change of sound speed with temperature.
US 2008/0200795, to Steckner, describes applying ultrasound at the MRI resonance frequency while making an MR image, for example at 0.3 tesla, where the resonance frequency would fall within the available ultrasound frequency range. The motion of the tissue in the ultrasound fields causes motion artifacts which affect the contrast of the MR image. Differences in the contrast of the MR image at different locations can be used to obtain information about the ultrasound absorption rate at different locations, since motion artifacts will be reduced in locations where the ultrasound does not penetrate as far into the tissue, due to greater absorption of ultrasound.
US 2010/0092424 to Sanghvi et al, describes applying high intensity focused ultrasound to a tumor so that it releases cellular material, and examining the released material to determine what kind of tumor it is.
U.S. Pat. No. 7,179,449 to Lanza et al, describes using an ultrasound contrast agent that binds to a target. The contrast agent has an ultrasound reflectivity that is temperature dependent. By changing the temperature, one can distinguish reflection of the ultrasound by the contrast agent, from reflection of the ultrasound from other structures in the body.
U.S. Pat. No. 6,824,518 to Von Behren et al, describes an ultrasound imaging transducer that interleaves occasional high power pulses among normal imaging pulses, to improve image quality. The temperature is monitored while using this transducer, to avoid damage to the tissue.
U.S. Pat. No. 5,935,075, to Casscells et al, describes using an infrared sensor in a catheter, in an IR fiberoptic system, optionally combined with an ultrasound image system, which detects plaque in arteries that is likely to rupture, by the extra heat such plaque produces. The method can also detect abnormal tissue or a foreign body that is cooler than the surrounding tissue. Casscells et al cites an earlier patent, U.S. Pat. No. 4,986,671, that to describes a catheter with an infrared sensor for measuring blood flow in a blood vessel. In U.S. Pat. No. 4,621,929, infrared radiation is directed along an optical fiber to heat an infrared sensor, and its subsequent cooling rate is used to measure the blood flow.
US 2007/0106157 to Kaczkowski et al describes using backscattered ultrasound to map the temperature of tissue which has been heated using ultrasound, or using any other heat source, as a function of time. The thermal diffusivity K, which can be anisotropic in regions of dense vasculature, and the heat source Q, as functions of position, are then calculated, and they are used for planning thermal therapy. Monitoring is done in real time, during thermal therapy, to see if Q has changed, due to changes in specific absorption, or changes in the intervening path attenuation, and if so, changes can be made in the heating power in real time, to compensate. Perfusion can also be measured non-invasively, and taken into account when monitoring the thermal therapy. These methods “can also be utilized as a general tissue characterization technique”, for modeling and monitoring thermal therapy.
U.S. Pat. No. 7,367,944 to Rosemberg et al describes monitoring a parameter indicating a biological response to heat, during thermal therapy, and discusses the role of perfusion in heat transport during thermal therapy.
US 2008/0004528 to Fitzsimmons et al describes using ultrasound to diagnose or characterize a target area by imaging it, to determine if it is benign or malignant, and to determine its size, geometry, vascularity, and/or density.
EP 1030611 to Baumgardner et al (CoolTouch, Inc.) describes diagnostic and therapeutic methods and techniques utilizing flushing and/or cooling, used in conjunction with energy delivery devices, including ultrasound. They describe sensing temperature, and using feedback loops for control. This is done when heating the dermis by a laser, while cooling the epidermis, in order to remove wrinkles.
US 2009/0287082 to Lizzi et al describes using ultrasound imaging to monitor heating and permanent effects in tissue, during application of therapeutic ultrasound.